Pharmacokinetic models are developed for the distribution and disposition of drugs, environmental contaminants, and endogenous metabolites in animals and man. They provide a plausible set of equations that can be used to extrapolate data from animals to man and thereby improve chemotherapy, and risk assessment. Emphasis has been placed on regional drug administration, and this has led to the development of spatially distributed models of drug transport in tissue. These analyses have provided considerable insight into the penetration depths of drugs administered intraperitoneally or by infusion into the brain. The penetration of cis-dichlorodiammine-platinum (II) (DDP) into peritoneal and subperitoneal tissue is being examined experimentally with an electron probe and the results compared with a reaction-diffusion equation of the process. A lumped model of DDP pharmacokinetics has been developed to include both metabolism to a mobile species and covalent binding to macromolecules. Pharmacokinetic theory which was developed for intra-arterial drug administration combined with hemoperfusion of vascular drainage had been validated experimentally in monkeys. Clinical trials further demonstrated the pharmacokinetic theory. Systemic exposure to BCNU was reduced by 56-87% compared with intra-arterial administration of the same dose. Studies with intracarotid infusion of indocyanine green have demonstrated the ability to remove a large fraction of the infused blood by pumping from the ipsilateral jugular vein.